The Serie A powerhouse have named previous Azzurri manager Spalletti to take the helm until the end of the season.
The experienced coach replaces Igor Tudor, who was sacked post the Lazio setback last weekend.
Tudor had joined the club in March as Thiago Motta's replacement but left after seven months after an eight-game winless streak.
Under Spalletti, Napoli clinched the Serie A championship in 2022-23 prior to assuming the Italy role, which missed out on the 2022 World Cup with Mancini at the helm.
Under his guidance, they made it to Euro 2024 where they were knocked out in the last 16 by Switzerland.
Yet, the Italian FA let Spalletti go in June post a qualifying defeat against Norway, with the Azzurri at risk of missing out on a third consecutive World Cup.
He has previously coached Inter Milan, Roma, and Udinese in Italy's top flight and lifted the Russian league trophy twice while at Zenit St Petersburg.
Massimo Brambilla took interim charge of Juventus during the 3-1 victory over Udinese on Wednesday which left them seventh in Serie A - trailing leaders Napoli by six points after nine matches.
They are 25th in the league phase of the Champions League, after recording one defeat and two ties in the initial three fixtures.
